Human erythropoietin (EPO) is a 166-aa glycoprotein which is involved in the proliferation and differentiation of erythroid progenitor cells. These cellular responses are mediated by the human EPO receptor (EPO receptor, EPOR), a 508-aa glycoprotein. EPO receptor is a protein of 508 amino acid length (Swiss Prot P19235) containing a single transmembrane domain and has been classified as a member of the growth hormone subfamily of class I cytokine receptors. EPO receptor is described, e.g., in Winkelmann, J. C., et al., Blood 76 (1990) 24-30, and Jones, S. S., et al., Blood 76 (1990) 31-35).
Antibodies against EPO receptor are known from, e.g., D'Andrea, A. D., Blood 82 (1993) 46-52; Elliott, S., Blood 107 (2006) 1892-1895; Kirkeby, A., J. Neurosci. Methods 164 (2007) 50-58; Miura, 0., Arch. Biochem. 306 (1993) 200-208; Mayeux, P., et al., J. Biol. Chem. 266 (1991) 23380-23385; Westphal. G., et al., Clin. Exp. Med. 2 (2002) 45-52; Elliott, S., et al., J. Immunol. Meth. 352 (2010) 126-139, and EP 1 146 056, EP 1 327 681, EP 0 773 962, EP 0 776 370, US 2002/0031806, US 2003/0215444, US 2004/0058393, US 2004/0071694, US 2004/0175379, US 2005/0227289, US 2005/0244409, US 2006/0018902, U.S. Pat. No. 6,153,190, U.S. Pat. No. 6,998,124, U.S. Pat. No. 7,053,184, U.S. Pat. No. 7,081,523, WO 1995/005469, WO 1996/003438, WO 2000/061637, WO 2004/035603, WO 2005/100403, and WO 2010/022924. However, studies investigating the expression and localization of EPO receptor in tissue samples produce divergent and often artifactual results because lack of specificity of known antibodies against EPO receptor (see Jelkmann, W., et al., Crit. Rev. One. Hematol. 67 (2008) 39-61; Elliott, S., et al., Blood 107 (2006) 1892-1895; Jelkmann, W. and Laugsch, M., J. Clin. Oncol. 25 (2007) 1627-1628; Kirkeby, A., et al., J. Neurosci. Methods 164 (2007) 50-58; Laugsch, M. et al., Int. J. Cancer 122 (2008) 1005-1011), or it was reported that studies employed antibodies with questionable specificity and the significance of the observations are controversial (Elliott, S. above).